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Antiinfective therapy in periodontics
1.
2. • The microbial etiology of inflammatory
periodontal diseases provides the rationale for
the use of antimicrobial medication in
periodontal therapy.
• As evidence for bacterial specificity in
periodontitis has accumulated and
strengthened over the past three decades,
dentists have increased their use of antibiotics
in periodontal therapy.
3. DEEP PERIODONTAL POCKET COMPLEX ROOT ANATOMIES
BACTERIAL TRANSLOCATION &
RECOLONIZATION
BACTERIAL INVASION
LIMITATIONS
Quirynen et al(2002)
5. Chemotherapeutic agent
• Chemotherapeutic agent is a general
term for a chemical substance that provides a
clinical therapeutic benefit
Anti-infective agent
• It is a chemotherapeutic agent that works
By reducing the number of bacteria present.
DEFINITIONS
6. Antibiotic
• An antibiotic is a naturally occuring ,semisynthetic or
synthetic type of antiinfective agent that destroys or
inhibits the growth of selective microorganisms,
generally at low concentrations.
Antiseptic
• An antiseptic is a chemical antimicrobial
agent applied topically or subgingivally to mucous
membranes, wounds or intact dermal surfaces to
destroy microorganisms and inhibit their reproduction
or metabolism
7. Disinfectant
• Disinfectants , a subcategory of antiseptics are
antimicrobial agents that are generally applied
to inanimate surfaces to destroy
microorganisms
9. Periodontal
patients who do
not respond to
conventional
mechanical
therapy,
for patients with
acute periodontal
infections
associated with
systemic
manifestations,
For prophylaxis in
medically
compromised
patients, and
as an adjunct to
surgical and non-
surgical
periodontal
therapy.
10.
11.
12.
13. Ideal antibiotic for prevention and treatment of
periodontal disease- Gibson et al 1982
Specific for
periodontal
pathogens
Allogenic and non
toxic
Substantive
Not in general use
for treatment of
other diseases
Inexpensive
14. Jorgensen and Slots -2000
Currently an ideal
antibiotic for the
treatment of
periodontal diseases
does not exist
15. Treatment of the patient based on
Patient’s clinical
status
Nature of the
colonising
bacteria
Risks and
benefits
associated with
the proposed
treatment plan
17. TETRACYCLINES
• Broad spectrum antibiotics
• Widely used in treatment of periodontal disease
• Ability to concentrate in periodontal tissues and inhibit the
growth of Aggregatibacter actinomycetamcomitans
• Anticollagenase effect-inhibit tissue destruction and aid bone
regeneration
• Entire tetracycline group of family exhibit anti collagenase
effect
• Tetracyclines were found to directly inhibit collagenases from
a wide variety of cells including PMN’s, macrophages,
osteoblasts, osteoclasts, chondrocytes, and malignant
melanoma cells (Golub et al 1987)
18. Pharmacology
• Naturally from streptomyces
• Semisynthetic
• Bacteriostatic – more effective against gram
positive than gram negative bacteria
• Concentration in GCF is 2-10 times that in
serum
19. Clinical use
Adjuncts in the
treatment of LAP-
eliminates tissue
bacteria,arrests
bone loss and
suppresses A.a
levels in
conjunction with
SRP
Increase in post
treatment bone
levels with this
method
Resistance ??!!
Long term use of low
antibacterial doses
of tetracyclines (250
mg /day for 2-7
years) showed
persistance of
pockets that did not
bleed on probing.
21. Tetracycline
• 250 mg-4 times a day
• Hence reduced compliance
• Inexpensive
SIDE EFFECTS
• GIT disturbances
• Photosensitivity
• Hypersentivity
• Increased blood
urea nitrogen
levels
• Blood dyscriasis
• Tooth
discolouration
22. Minocycline
• Effective against a broad spectrum of
microorganisms
• Suppresses spirochetes and motile
rods as effective as SRP,evident upto
3 months
• Can be given twice daily-more
compliance compared to tetracycline
• Less phototoxicity and renal toxicity
• May cause reversible vertigo
23. Ciancio et al 2000
Minocycline administered 200
mg/day for 1 week results in a
reduction in total bacterial
counts, complete elimination
of spirochetes for upto 2
months, and improvement in
all clinical parameters
24. Doxycycline
• Similar to minocycline and equally
effective (Ciancio 1990)
• Can be given only once daily
• More patient compliance
• Absorption from GIT only slightly
altered by calcium, metal ions or
antacids
• 100mg bid for first day then 100
mg qd
• To reduce GI upset 50 mg can be
taken bid
26. HOST MODULATION
• SDD is approved by US FDA, UK Medicines &
Healthcare Products Regulatory Agency
• PERIOSTAT (CollaGenex Pharmaceuticals Inc.
Newtown PA)
27. To avoid antibiotic resistance, SDD preparation was introduced
containing 20mg of doxycycline(Golub1990)as opposed to
50/100mg dose that is available for antibiotic purposes
Not used as monotherapy, Used as an adjunct to SRP
Taken as 20mg twice daily for 3 months and up to a maximum
of 9 months
Three month prescription fits well with the typical maintenance
recall of 3 months.
28. Metronidazole
Nitroimidazole compound
developed to treat
protozoal infections
Bactericidal to anerobic
organisms and is believed
to disrupt bacterial DNA
synthesis in conditions with
a low reduction potential
Not the drug of choice in
Aa infections-yet may be
effective at therapeutic
levels because of its
hydroxy metabolite
Metronidazole also
effective against anerobes
like P.gingivalis and
P.intermedia
29. Rams et al 1992
Combination therapy
using metronidazole
is effective against Aa
infections
31. A single dose of
metronidazole-250 mg
orally appears both in
serum and GCF in
sufficient quantities to
inhibit a wide range of
suspected periodontal
pathogens.
Administered
systemically 750-
1000mg/day for 2
weeks, metronidazole
reduces the growth of
anerobic flora,
including spirochetes
and decreases the
clinical and histological
signs of periodontitis
Most common
regimen 250 mg tid
for 7 days
32. Use of metronidazole in
refractory periodontitis
more effective than
placebo
Combination with
amoxicillin or
amoxicillin clavulanate
potassium (Augmentin)
metronidazole may be
of value in the
management of
patients with LAP or
refractory periodontitis
SRP +Metronidazole
significantly reduced
the need for surgery
compared to root
planing alone
33. Side effects of metronidazole
Antabuse effect when
alcohol is ingested
Inhibits warfarin
metabolism
Should be avoided in
patients who are taking
lithium
36. Amoxicillin
• Semisynthetic penicillin with extended
antiinfective spectrum
• Excellent absorption after oral administration
• Is susceptible to penicillanase and β lactamase
that breaks the ring structure and renders
them ineffective
• Recommended dosage is 500mg tid for 8
days
37. Amoxicillin clavulanate
potassium
• Resistant to penicillinase enzymes produced
by some bacteria
• Useful in the management of patients with
LAP and refractory periodontitis (Rams et al
1992)
38. Bueno et al 1988
Augmentin halted
alveolar bone loss in
patients with periodontal
disase that was refractory
to treatment with other
antibiotics
39.
40. Pharmacology
• Macrolides contain a many membered lactone
ring to which one or more deoxy sugars are
attached.
• Inhibit protein synthesis by binding to the 50s
ribosomal subunits
• Can be bacteriostatic or bactericidal
• Depending on concentration of the drug and
nature of the microorganism
42. Spiramycin
• Effective against gram positive organisms and
it is excreted in high concentrations in saliva
• Has minimal effect on increasing attachment
levels
43. Azithromycin
• Member of the azalide class of macrolides
• Effective against anerobes and gram negative
bacilli
After an oral dosage of 500 mg once daily
for 3 days significant levels can be
Detected in most tissues for
7-10 days
The conc., of azithromycin in
tissue specimen from
periodontal lesions is
significantly higher than that
of normal gingiva
44. Penetrates fibroblasts and phagocytes in
concentration 100 to 200 times greater than
that of extracellular compartment
Azithromycin is actively transported to
sites of inflammation by phagocytes,
then released directly into sites of
inflammation as phagocytes ruptures
during phagocytosis
45.
46. • Clindamycin is effective against anerobic bacteria
• Effective in situations in which patient is allergic
to penicillin
Clinical use
• Clindamycin has shown efficacy
in patients with periodontitis
refractory to tetracycline
therapy
• Walker et al showed that
clindamycin assisted in
stabilizing refractory patients
dosage was 150 mg qid for 10
days
• Jorgensen and Slots recommend
a regimen of 300mg bid for 8
days
Side
effects
Pseudomembranous
colitis
47.
48. Pharmacology
Ciprofloxacin is a quinolone active against gram
negative rods, including all facultative and anerobic
putative periodontal pathogens
Clinical
use
• Minimal effect on streptococcus species
• All strains of Aa are suseptible
• Also used in combination with metronidazole
49. Side effects
• Nausea , headache, metallic
taste in the mouth and
abdominal discomfort have
been associated with
ciprofloxacin
• Quinolones inhibit the
metabolism of theophylline
and caffeine and concurrent
administration can produce
toxicity.
• They also enhance the effects
of warfarin and other
anticoagulants
57. Antibiotic prophylaxis for SABE
All dental procedures that involve
manipulation of gingival tissue or the
periapical region of teeth, or perforation of
the oral mucosa.
58. Antibiotic prophylaxis is NOT
recommended for the following
dental procedures or events:
routine anesthetic
injections through
noninfected tissue;
taking dental
radiographs;
placement of
removable
prosthodontic or
orthodontic
appliances;
adjustment of
orthodontic
appliances;
placement of
orthodontic brackets;
shedding of
deciduous teeth
bleeding from
trauma to the lips or
oral mucosa.
59.
60. Antibiotic prophylaxis -AHA
Situation Agent
Regimen – Single dose 30–60 minutes before
procedure
Adults Children
Oral Amoxicillin 2 gm 50 mg/kg
Unable to take oral medication
Ampicillin
OR
2 g IM or IV* 50 mg/kg IM or IV
Cefazolin or ceftriaxone 1 g IM or IV 50 mg/kg IM or IV
Allergic to penicillins or ampicillin –
Oral regimen
Cephalexin**† 2 g 50 mg/kg
OR
Clindamycin 600 mg 20 mg/kg
OR
Azithromycin or clarithromycin 500 mg 15 mg/kg
Allergic to penicillins or ampicillin
and unable to take oral medication
Cefazolin or ceftriaxone†
OR
1 g IM or IV 50 mg/kg IM or IV
Clindamycin 600 mg IM or IV 20 mg/kg IM or I
61.
62. • Local antimicrobial therapy in periodontitis
involves direct placement of an antimicrobial
agent into subgingival sites, minimizing the
impact of the agents on nonoral body sites
63. What happens when antibiotic
reach the biofilm surface?
(ANTIBIOTIC RESISTANCE)
Biofilm cells – 1000 to 1500 times resistant to antibiotics
Exopolysaccharide is produced by bacteria where enzymes are
concentrated through which the drugs cannot penetrate.
Antibiotics cannot penetrate the depth and do not reach
colonies at the depth of the matured biofilm.
67. • It is a topical antiseptic belonging to the
family of bisguanides
• It is bacteriostatic at lower and
bactericidal at higher concentrations
• A biodegradable CHX chip (PerioChip)
• composed of hydrolysed gelatin matrix,
cross linked with glutaraldehyde,
glycerine and water
• Chip is 5 mm long, 4 mm wide with 2.5
mg of chlorhexidine gluconate
• Average drug concentration in the GCF
greater than 125 µg ml for 7–10 days
68.
69. 23 cm in length and 0.5
mm in diameter
25% of Conc
(12.5 mg)
flexible, and can be
folded on itself
Delivery Device is
ethylene vinyl Acetate
monolithic fibers
Non resorbable
• a concentration of
1, 300µg/ml for a
period of 7 days
Release of tetracycline
for 10 days
Bacteriostatic
Time consuming (10
min per tooth)
Removal of fiber after
10 days
oral candidiasis
70. Types of fibers
• Hollow fibers: cellulose acetate fibers are filled with
tetracycline and they provide only sustained release system.
• Monolithic fibers: prepared by melt extrusion technique,
wherein, a mixture of 25% tetracycline HCl and 75% ethylene
vinyl acetate was heated to 214 C and extruded as 0.5 mm
fiber and they provide a controlled release system
• Resorbable fibers: described a device in which tetracycline is
incorporated into cross-linked collagen matrix, atelocollagen,
capable of delivering tetracycline in the crevicular fluid at
therapeutic levels for upto 10 days after insertion and drug
levels ranged from 17 to 180µg/ml.
71.
72. Atridox
Doxycycline gel 10%
Biodegradable
hardens when
placed in
periodontal pocket
Contains by wt
10%DOXY , 33% poly
dilactide and
57% N- methyl-2
pyrrolidone
Controlled delivery
device -7 days
It inhibits bacterial
protein synthesis
Bacteriostatic
Resorbable
8-10 weeks
75. Bio-degradable powder in syringe
microspheres
Each microsphere contain 1mg of antibiotic
Resorption in 21 days
Minocycline Hydrochloride 1%
76. • Film
• ethylcellulose containing 30% of minocycline cast from
ethanol, chloroform or chloroform with polyethylene
glycol were tested ass sustained release devices
• Microspheres:
• Minocycline micro-encapsulated in a resorbable poly
(glycolide-lactide) slow release polymer (Braswell et al),
this can be administered by means of disposable plastic
syringe. The volume of microspheres in each syringe is 4
mg which is equivalent to 1 mg of minocycline base.
80. ISSUE SYSTEMIC LOCAL
Route of administration Oral/ parentral Site specific
Drug distribution Wide distribution Narrow range
Therapeutic potential May reach widely
distributed micro
organisms better
May act better locally on
biofilm associated bacteria
Problem Systemic side effects Reinfection from nontreated
sites
Clinical Limitations Requires good patient
compliance
Reinfections limited to the
treated site
Diagnostic problems Identification of
pathogens, choice of
drug
Distribution pattern of lesion &
pathogens, identification of
sites to be treated
Pain/discomfort Not painful Nil
Drug Dosage Higher drug dosage (mg) Lower Dosage
81. Peaklevels Few hours in plasma Within few minutes in GCF
Frequency Once in 6-12 hrs Once a week
Super infection Present Limited
Microbial resistance Present Limited
Time required Less time Longer if many sites are treated
Effects on connective tissue
Associated plaque
Effective Limited
83. Conclusion
• The current data suggest that Systemic and local
delivery of antimicrobials into the periodontal pocket
can improve periodontal health. However, they do
not provide a superior result to scaling and root
planing.
• In conjunction with scaling and root planing, the
adjunctive use of antimicrobial agentsmay enhance
the results in sites which do not respond to
conventional therapy